Hippenmeyer Group

Genetic Dissection of Cerebral Cortex Development

The human brain, of which the cerebral cortex is the largest structure, is composed of a sophisticated network of billions of interconnected neurons. Precise mapping of the cortical architecture is an essential starting point to learn how cortical circuits account for behavior and cognitive activity, and how alterations in the cytoarchitecture might lead to neurological and psychiatric disorders or dementia. We use multidisciplinary approaches including the genetic MADM (Mosaic Analysis with Double Markers) technology with the aim to trace the logic of how individual neurons successively build up the cortical entity during development. MADM technology offers an unparalleled method to visualize and concomitantly manipulate sparse clones and small subsets of genetically defined neurons at the single cell level in mice. In other words, if one imagines looking at a forest afar it is very difficult to recognize the trimming of a single branch of an individual tree. However, when a single tree stands lonely in a field one can easily observe the snip of even the finest branches of that tree. Similarly, with the MADM method we can now navigate through the dense brain meshwork and follow individual neurons and their fine branches in differently shining red and green colors. An added critical feature of MADM is the possibility to not only label single cells but at the same time also pursue genetic manipulations: it is feasible to label certain neurons that are wild-type in one color, say green. At the same time, MADM can also label in red genetically mutant neighboring sisters of the ‘healthy’ green cells. This allows comparison of wild-type and mutant neurons side by side. We apply MADM to study the fundamental cellular, molecular and epigenetic mechanisms underlying the critical neurodevelopmental processes that control the assembly of the cortex cytoarchitecture.

We are currently looking for postdocs and PhD students. Candidates with a strong background in Molecular Biology are particularly encouraged to apply. Experience with next generation sequencing, live-imaging, human organoid culture or mouse genetics is an asset. Postdoc candidates send their application including CV, and statement of motivation and research interests to simon.hippenmeyer@remove-this.ist.ac.at. PhD student candidates should apply directly at the IST Austria Graduate School.